Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials.

AIM: To evaluate the safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab according to diabetes mellitus status. METHODS: Safety data from 14 trials (8-104-week durations) were analysed by treatment (alirocumab or placebo/ezetimibe control) and diabetes status (yes/no, defined by medical history). Adverse event data were assessed using descriptive statistics and Cox models. RESULTS: Of the 5234 trial participants, 1554 (29.7%) had diabetes. Overall, treatment-emergent adverse events were similar in the alirocumab and control groups, except for more frequent local injection site reactions with alirocumab. Fewer people with diabetes experienced local injection site reactions [alirocumab, 3.5%, control, 2.9%; hazard ratio 1.24 (95% CI 0.68-2.25)] than those without diabetes [alirocumab, 7.5%; control, 4.9%; hazard ratio 1.51 (95% CI 1.13-2.01)]. Those with diabetes reported a greater number of serious adverse events (alirocumab, 19.4%; control, 19.7%) than those without diabetes (alirocumab, 14.5%; control, 13.5%). In people with diabetes, major adverse cardiac events occurred in 2.7% of alirocumab-treated people [control, 3.3%; hazard ratio 0.74 (95% CI 0.41-1.35)]; in those without diabetes, 1.8% of alirocumab-treated people had major adverse cardiac events [control, 1.7%; hazard ratio 0.95 (95% CI 0.56-1.62)]. Overall, no increase in HbA1c or fasting plasma glucose vs control treatment groups was observed, regardless of diabetes status. CONCLUSION: This pooled analysis across 14 trials demonstrated similar safety for alirocumab vs control treatment, irrespective of diabetes status, except for more frequent local injection site reactions with alirocumab. People with diabetes reported fewer local injection site reactions than those without diabetes.

Why is endometrial cancer less common in Greece than in other European Union countries?

Among European countries, Greece has the lowest incidence of and mortality from endometrial cancer. We have undertaken a case-control study aiming to identify possible reasons for this. Cases were 84 women with histologically confirmed incident endometrial cancer, whereas controls were another 84 women with intact uterus admitted for small gynaecological operations, mainly pelvic prolapse. Women provided information concerning socio-economic, reproductive and medical variables. Most findings were in line with those previously reported from other investigations; no association was as striking as to suggest an effect modification that could underlay the favourable position of Greece with respect to endometrial cancer. Novel findings were the statistically significant inverse associations of endometrial cancer with coffee drinking and suggestive inverse associations with height-induced abortions. Low average height of Greek women, high frequency of induced abortions and low frequency of replacement oestrogens use may contribute to the lower endometrial cancer incidence in Greece.

Consumption of vegetables, fruit and other plant foods in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries.

OBJECTIVE: To describe and compare the consumption of the main groups and sub-groups of vegetables and fruits (V&F) in men and women from the centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cross-sectional analysis. Dietary intake was assessed by means of a 24-hour dietary recall using computerised interview software and standardised procedures. Crude and adjusted means were computed for the main groups and sub-groups of V&F by centre, separately for men and women. Adjusted means by season, day of the week and age were estimated using weights and covariance analysis. SETTING: Twenty-seven centres in 10 European countries participating in the EPIC project. SUBJECTS: In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, randomly selected from each EPIC cohort. RESULTS: The centres from southern countries had the highest consumption of V&F, while the lowest intake was seen in The Netherlands and Scandinavia for both genders. These differences were more evident for fruits, particularly citrus. However, slightly different patterns arose for some sub-groups of vegetables, such as root vegetables and cabbage. Adjustment for body mass index, physical activity, smoking habits and education did not substantially modify the mean intakes of vegetables and fruits. CONCLUSIONS: Total vegetable and fruit intake follows a south-north gradient in both genders, whereas for several sub-groups of vegetables a different geographic distribution exists. Differences in mean intake of V&F by centre were not explained by lifestyle factors associated with V&F intake.

Total cholesterol and HDL-cholesterol in relation to socioeconomic status in a sample of 11,645 Greek adults: the EPIC study in Greece. European Prospective Investigation into Nutrition and Cancer.

OBJECTIVE: To examine the relationship between educational level, a powerful indicator of socioeconomic status in Greece, total cholesterol and HDL-cholesterol in a large sample of Greek adults. METHODS: The study sample consisted of 11,645 subjects, 4,398 men and 7,247 women, aged 23-86 years, who voluntarily participated in the Greek component of the EPIC study during 1994-98. Educational attainment was divided into low, medium, and high. Linear regression analyses were performed, in men and women separately, using total and HDL-cholesterol as dependent variables and educational level as independent, while controlling for age. RESULTS: Total blood cholesterol values are inversely associated with educational level in both genders, a pattern contrasting with that found 20 years ago. The association is more prominent among women. HDL-cholesterol values are inversely associated with educational level in men, whereas the association is less consistent in women.

Pulmonary embolism from in situ right atrial thrombus after coronary artery bypass surgery.

Pulmonary embolism after cardiac surgery is attributed to embolization from thrombus within the deep venous system. We report two cases of pulmonary embolism after coronary artery bypass surgery in which transesophageal echocardiography detected in situ right atrial thrombus. The right atrium should be screened for thrombus in patients who have pulmonary embolism after cardiac surgery.

Risk of catheter-related emboli in patients with atherosclerotic debris in the thoracic aorta.

The aim of this study was to evaluate the risk of performing cardiac catheterization or intraaortic balloon pump placement in patients with transesophageal echocardiographically detected atherosclerotic aortic debris. Cardiac catheterization was performed in 70 patients with atherosclerotic aortic debris (in 11 via the brachial approach and in 59 via the femoral approach) and in 71 control patients. An embolic event occurred in 10 (17%) of 59 patients with atherosclerotic aortic debris after femoral catheterization compared to 2 (3%) of 71 control patients without atherosclerotic aortic debris (p = 0.01). None of the 11 patients with atherosclerotic aortic debris who underwent brachial catheterization had an embolic event. An intraaortic balloon pump was placed in 10 patients with atherosclerotic aortic debris and in 12 control patients. An embolic event related to placement of the intraaortic balloon pump occurred in 5 (50%) of 10 patients with atherosclerotic aortic debris; no control patient had an embolic event (p = 0.02). Patients with mobile atherosclerotic aortic debris were at the highest risk for catheter-related embolism. The strongest clinical predictors of atherosclerotic aortic debris were advanced age and peripheral vascular disease. Transesophageal echocardiographic recognition of atherosclerotic aortic debris identifies patients at high risk of stroke or peripheral embolism after cardiac catheterization or intraaortic balloon pump placement. If the aortic debris is mobile, the risk is particularly high. When atherosclerotic aortic debris is detected, especially if the debris is mobile, substituting brachial for femoral catheterization and avoiding placement of an intraaortic balloon pump may reduce the risk of embolism.

Endocarditis-associated paravalvular abscesses. Do clinical parameters predict the presence of abscess?

STUDY OBJECTIVE: To determine whether standard clinical and transthoracic echocardiographic criteria considered to be suggestive of the presence of endocarditis-associated paravalvular abscess are predictive of which patients would benefit from reliable but invasive transesophageal echocardiographic investigations for abscess. DESIGN: Retrospective chart review. SETTING: A 630-bed university hospital. PATIENTS: Forty-eight patients with 51 episodes of definite endocarditis and 24 paravalvular abscesses. MEASUREMENTS AND RESULTS: A comparison of abscess and nonabscess populations revealed that clinical parameters (patient demographics, valvular involvement, presence of a prosthesis, infection with a virulent organism, pericarditis, persistent fever, persistent bacteremia, congestive heart failure, history of intravenous drug use, embolization) and transthoracic echocardiographic parameters were insensitive predictors of the presence of abscess. The only statistically significant correlate was the presence of previously undetected atrioventricular or bundle branch block. Paravalvular abscesses were common in our population and were associated with increased mortality. Improved survival correlated with the absence of mitral valve involvement and the absence of moderate-to-severe congestive heart failure. CONCLUSIONS: Given the accuracy and safety of transesophageal echocardiography and the unreliability of clinical and transthoracic echocardiographic criteria, we recommend that transesophageal echocardiography be considered in all endocarditis patients with previously unrecognized conduction disturbances, aortic or prosthetic valve involvement, or both, or indications for valve replacement, or all of the foregoing.

Spontaneous arterial embolization after thrombolytic therapy for acute myocardial infarction: the role of transesophageal echocardiography.

Arterial embolization from thrombolytic therapy for acute myocardial infarction is rare. We report two cases of spontaneous arterial embolization following the use of tissue plasminogen activator for acute myocardial infarction. Transesophageal echocardiography was able to identify the source of embolism as mobile atherosclerotic debris within the thoracic aorta. This information was of value in the management of these patients, in that femoral catheterization which could have precipitated further embolization was avoided.

The role of echocardiography in blunt chest trauma: a transthoracic and transesophageal echocardiographic study.

Previous studies assessing the value of transthoracic echocardiography (TTE) in blunt chest trauma are limited because patients with severe chest wall injury often have suboptimal echocardiographic findings. Transesophageal echocardiography (TEE) can provide high quality images when the transthoracic image quality is poor. To provide complete echocardiographic assessment of cardiac structure and function we prospectively performed TTE in 105 patients with severe blunt chest trauma and TEE in 20 of the 105 patients (19%) whose TTE examination results were suboptimal. Myocardial contusion was diagnosed in 31 patients (30%), 22 by TTE and nine by TEE. Cardiac complications developed in 8 of 31 patients (26%) with myocardial contusion compared with 2 of 74 patients (3%) with normal echocardiographic findings (p = 0.001). Cardiac complications required treatment in only four patients. Echocardiography was of value in detecting severe right ventricular dysfunction as the cause of hypotension in two patients with suspected cardiac tamponade. Four patients with myocardial contusion died compared with two patients with normal echocardiographic findings (p = NS). No death was related to the cardiac status. In addition, TEE detected aortic injury in five patients, four with focal intimal tears and one with an aortic transection. We conclude that myocardial contusion is common following blunt chest trauma, rarely requires treatment, and is associated with a favorable prognosis. Only patients who develop cardiac complications benefit from echocardiography. Transesophageal echocardiography is of value when the TTE examination results are suboptimal and when aortic injury is suspected.

Severe right ventricular contusion mimicking cardiac tamponade: the value of transesophageal echocardiography in blunt chest trauma.

Clinically, severe right ventricular contusion may mimic cardiac tamponade. We report two cases of suspected cardiac tamponade after blunt chest trauma in which the diagnosis of severe right ventricular contusion was made only by transesophageal echocardiography, avoiding unnecessary and hazardous pericardiocentesis. These cases illustrate the value of transesophageal echocardiography in diagnosing blunt chest trauma.

The effect of Mycoplasma arthritidis infection on the kinetics of colloidal carbon clearance in mice.

The activity of phagocytes from A/J mice was estimated by the carbon clearance test following injection of Mycoplasma arthritidis. Phagocytic activity was significantly depressed 12 h post-infection (P = 0.001) and returned to normal values at 24 h. For animals examined 2 and 7 days post-infection, the overall phagocytic activity increased significantly (P < 10(-4). Phagocytic activity gradually decreased and returned to that of the control group by the end of the fourth week. The relative weights of liver and spleen were significantly increased from the 2nd day post infection (P = 0.0028 and P = 0.0014 respectively) and remained increased until the end of the experiment. The early depressive effect on phagocytic activity may be related to superantigen activity with the production of mediators such as macrophage deactivating factor. The later expansion of the macrophage population might bring about the stimulation of autoreactive clones of T and B cells and be responsible for the chronic arthritis that developed in the mycoplasma treated mice.

The role of transesophageal echocardiography in the acute onset of paraplegia.

BACKGROUND AND PURPOSE: Acute paraplegia must be investigated promptly to exclude reversible causes. In this report we illustrate the usefulness of transesophageal echocardiography in identifying the vascular etiologies of acute paraplegia. CASE DESCRIPTIONS: Two patients presented with acute paraplegia, one spontaneously and the other after removal of an intra-aortic balloon pump catheter. Through the use of transesophageal echocardiography, we excluded aortic dissection and identified protruding atherosclerotic plaques in the descending thoracic aorta of each patient. Embolization of atheromatous material from the thoracic aorta was considered the most likely etiology of paraplegia in both cases. CONCLUSIONS: Embolization from atherosclerotic plaques in the thoracic aorta may be an underestimated cause of acute paraplegia. Transesophageal echocardiography provides a safe, rapid, and reliable tool for investigating a vascular etiology of acute paraplegia.

Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans.

Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 micrograms/kg, to 22 patients with chronic congestive heart failure (ejection fraction less than 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 micrograms/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 micrograms/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 micrograms/kg dose. The cardiac index was reduced by the 158 micrograms/kg dose, but increased after 251, 398, and 630 micrograms/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 micrograms/kg dose level.(ABSTRACT TRUNCATED AT 250 WORDS)